1. Field of the Invention
The present invention provides a 5-protected aminopyrimidine compound, which is used as an intermediate for various compounds having a pharmacological activity, a production method thereof and an intermediate therefor.
2. Discussion of the Background
A 5-protected aminopyrimidine compound serves as an intermediate for the synthesis of various compounds having a pharmacological activity. These compounds include anticancer agents, NK1 antagonists, elastase inhibitors and the like (U.S. Pat. No. 6,380,206 and WO02/42280).
A method for introducing an amino group into the 5-position of pyrimidine has been known. This known method consists of introducing a nitro group into uracil, and then reducing the same (J. Chem. Soc., 1565-1570, 1951).

However, the volatility of nitro compounds has lead to a general reticence for use in an industrial production method. In addition, since uracil derivatives have a carbonyl group at both the 2-position and the 4-position, position selective introduction of a substituent into the 2-position or the 4-position is difficult (J. Chem. Soc. Perk. Trans. 1, (7), 919-922, 1992, EP647639A and Tetrahedron, 58 (11) 2147-2153, 2002).
A method of producing an aminopyrimidine compound by using a compound other than uracil as a starting material is known. In this known method, glycine ethyl ester is reacted with ethyl formate and sodium methoxide to produce an ethyl-α-formyl-formyl glycinate sodium salt, which is reacted with an acid addition salt of amidine in methanol to result in formylaminopyrimidine (Collect. Czech Chem. Comm., 51(1), 215-233, 1986).
As a different production method, the production method shown in the following reaction scheme has been reported (J. Chem. Soc. Perk. Trans. 1, (7), 1659-1664, 1988):

wherein Ph is a phenyl group, Et is an ethyl group, Bz is a benzyl group.
However, the production yields resulting from this method are often unsatisfactory. Moreover, when an amino group at the 5-position of an aminopyrimidine compound is protected with an aliphatic acyl group, deprotection can be conducted under comparatively mild conditions, but a compound having the 2-position (e.g., 2-phenyl-4-ethoxymethylene-azlactone, which is a starting material to be used for this reaction) as an aliphatic group can be obtained only in a comparatively low yield (WO03/106434).
Accordingly, there remains a critical demand for a method of preparing intermediates for anticancer agents, NK1 antagonists, elastase inhibitors in which the process comprises efficient production of a 5-protected aminopyrimidine compound represented by (5), as well as a method that enables the preparation of the desired intermediate in high yield and high purity.